OpenBiome Announces New Direct Testing for SARS-CoV-2 in Fecal Microbiota Transplantation (FMT) Preparations and Release of New Inventory
Pending completion of stool-based testing for SARS-CoV-2, OpenBiome will expand investigational FMT availability from emergency use to any scheduled patient
OpenBiome is phasing out production of new treatments. It aims to have inventory to meet demand throughout 2021, as a bridge to FDA-approved therapies
CAMBRIDGE, Mass. – OpenBiome will expand availability of investigational FMT preparations for all scheduled patients, effective May 3, 2021. All material collected from donors since December 1, 2019 will be qualified using a new direct test for the presence of SARS-CoV-2, the virus that causes COVID-19.
Since July 2020, OpenBiome has only been shipping FMT preparations for emergency use from limited inventory manufactured prior to December 1, 2019. In keeping with guidance from the U.S. Food and Drug Administration (FDA), this new direct test allows OpenBiome to now qualify inventory produced in 2020 for clinical use. It supplements ongoing measures that OpenBiome has performed to surveil donor health.
During 2020, OpenBiome, like many organizations, experienced rising costs and significantly reduced revenues throughout the pandemic. The fixed costs associated with maintaining our manufacturing platform rose, while our ability to produce new treatments, and make them available to patients, was challenged by the need for novel stool-based SARS-CoV-2 screening methods to meet our quality and safety standards and to qualify products for patient use.
In navigating this financial situation, along with the anticipated near-term arrival of FDA-approved alternatives to FMT, we made the difficult decision in November to begin phasing out manufacturing of new FMT treatments and sell equipment and related manufacturing assets. This change is necessary to support operating costs in 2021 and will best position OpenBiome to continue serving patients for whom FMT addresses an unmet medical need, while recognizing the diminished long-term need for investigational FMT after a microbiome-based product gains FDA approval.
OpenBiome’s goal for the next year is to continue providing investigational FMT until patients have access to an FDA-approved treatment for recurrent C. difficile.
We have manufactured a large supply of FMT treatments that will undergo direct testing for SARS-CoV-2. This new test, which has been implemented with review by the FDA, is part of OpenBiome’s recent changes to its donor screening program to mitigate the risk of transmission of infectious agents, including SARS-CoV-2. The test—developed by CosmosID, a provider of bioinformatics software and laboratory services for microbiome R&D and infectious disease applications—allows OpenBiome to make FMT treatments manufactured since December 1, 2019 available for patient use.
Upon completion of SARS-CoV-2 testing, OpenBiome plans to start fulfilling orders for any scheduled patients who are eligible for FMT on May 3, 2021. We will provide email notifications to clinical partners and updates on our website as this policy takes effect.
Since 2013, OpenBiome’s nonprofit mission has been to expand safe access to FMT—a crucial but investigational treatment for the thousands of C. difficile patients who fail antibiotics each year—and to catalyze research on the human microbiome. OpenBiome has, above all, sought to offer a solution to address this urgent, unmet need until the arrival of FDA-approved alternatives. With announcements this past summer that new drug candidates have delivered positive results in pivotal trials, we anticipate the arrival of FDA-approved microbiome-based treatments in the near future.
In 2021, beyond working to make our extensive existing inventory available for patient use, OpenBiome will be building on our work supporting over 50 clinical trials to translate our growing understanding of the human gut microbiome into advancements for public health.
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Update March 7, 2021: We have additional updates and information to answer questions that we have received since our announcement. You may skip to the new content here. Please feel free to reach out for any additional information that would be helpful, and we will continue to build out this list. You may reach us at email@example.com.
Can patients receive an OpenBiome FMT preparation now? Until May 3, 2021, OpenBiome will be fulfilling orders for urgent use only. Partner physicians may place an order by sending a completed Emergency FMT Order form to firstname.lastname@example.org. More information can be found on our Ordering Emergency Use FMT Preparations webpage.
If you are a patient considering a fecal transplant, we recommend discussing FMT with your physician to determine whether it is the right choice for your treatment. More information on FMT can be found on our Patient Support Webpage. For patients looking for a physician, our Find A Doctor tool can help locate an OpenBiome-partnered clinician in your area.
When will OpenBiome be able to fulfill FMT orders for non-emergency cases? OpenBiome plans to begin shipping FMT treatments for non-emergency cases on May 3, 2021. Existing clinical partners will receive an email update when this service has resumed, and a notice will be posted on our website at www.openbiome.org.
We will require that physicians requesting an FMT confirm the following criteria:
Each FMT preparation is requested for an identified patient who is scheduled or awaiting scheduling to undergo an FMT.
Each scheduled patient has an active diagnosis of C. difficile infection (CDI) that has failed to respond to at least two courses of standard-of-care antibiotic therapy for mild or moderate CDI OR has severe/fulminant CDI that has failed standard-of-care antibiotic therapy.
Existing clinical partners may request multiple FMT preparations. However, each unit must be for a unique eligible patient who meets the criteria above. Eligibility criteria is based on FDA guidance regarding the use of investigational FMT under enforcement discretion.
How does the stool-based SARS-CoV-2 test work? The test, which was developed by CosmosID, uses RT-PCR, the same molecular technique used in COVID-19 diagnostic testing such as nasopharyngeal swab testing, to check for the presence of SARS-CoV-2 genetic material in donor stool. CosmosID, a Rockville, MD-based provider of industry-leading bioinformatics software and laboratory services for microbiome R&D and infectious disease applications, is directly testing each stool donation that was processed into FMT preparations.
For how long will OpenBiome continue to provide FMT preparations? We have considerable inventory, which should allow us to continue to supply FMT for C. difficile infection until at least the end of 2021. Although there is no guarantee, we hope that there will be broader access to FDA-approved microbiome-based therapies around that time. We are also continuing to support existing clinical trial collaborations and will also support new single-patient investigational new drug (SPIND) requests.
Why is OpenBiome phasing out the manufacturing platform now? Why not wait until new FDA-approved products are available? OpenBiome launched in 2013 to offer investigational FMT as an immediate solution to an urgent, unmet need while recognizing that our services would eventually be replaced by FDA-approved alternatives. Although we planned for a smooth transition away from large-scale stool banking, the pandemic accelerated our timelines and presented additional challenges—such as the need to directly screen our inventory using a stool-based SARS-CoV-2 test and maintaining our manufacturing platform through a prolonged period of significantly reduced revenues.
Navigating these challenging situations required us to take the actions outlined below:
In March 2020, to mitigate the potential risk of transmission of SARS-CoV-2 via FMT, we quarantined all FMT material collected on or after December 1, 2019 until we had a direct stool-based test for SARS-CoV-2 that was accepted by the FDA for this purpose.
Since July 2020, to make the best use of a very limited supply of material collected prior to December 2019, we have been providing FMT only for the most urgent cases. At the time, we had no visibility into when—if ever—we would be able to provide FMT material collected after December 2019 for patient use.
By November 2020, we faced a difficult decision. Unless we dramatically reduced costs, we risked running out of money before we could release our remaining inventory that was manufactured after December 1, 2019. We decided to sell equipment, software, and other assets, to our longtime collaborator, Finch Therapeutics. This sale provided us with the financial resources we needed to continue to develop a suitable SARS-CoV-2 test.
Fortunately, we have now received confirmation from FDA that our proposed testing methods for SARS-CoV-2 are sufficient to begin releasing our current inventory. We are implementing this test across our inventory to release it for use in patients later this year.
The announcement mentioned providing access to FMT until new FDA-approved products are available. Does OpenBiome have special insight into when new products will be available? No, OpenBiome does not have any special insight into the FDA’s regulatory process. We’re inferring from announcements made this past summer of positive data from three pivotal trials. These indicated that there could soon be multiple products approaching the finish line, and we assume that at least one will successfully gain FDA approval. Given this news, and the fact that these products also have FDA breakthrough designation, which would accelerate review timelines once a biologics license application is filed, we expect to see an approval in 2022.
What happens if OpenBiome runs out of material before alternatives are available? What will patients, clinicians and researchers who want to continue to use FMT do next? There are two things we are doing now to address this need:
We have considerable inventory on hand. We aim to enforce close stewardship of inventory by shipping only for scheduled patients. If needed, we will consider further restrictions to help protect supply for the most urgent cases.
In the future, we anticipate that access to FMT for clinical use will be met by a decentralized network of hospital- and university-run stool banks. To support this network, we are working to create a library of information about stool banking, to open source our protocols and adapt them for institutional stool banking contexts, later this year. When it comes to FMT research, OpenBiome supplies approximately 30% of current trials listed on clinicaltrials.gov – existing institutional stool banks drive the bulk of FMT research. We think we can help enhance these operations by sharing our experiences.
When will OpenBiome resume shipping, and why can’t it ship now, since the SARS-CoV-2 test is cleared? We plan to resume shipping for scheduled patients on May 3, 2021. We need to complete direct testing of our FMT treatments manufactured since December 1, 2019 with a stool-based assay for SARS-CoV-2 before we can support broader FMT use again. While the test has been accepted by the FDA, it will take time to appropriately implement across every lot in our inventory. Until then, we are providing FMT preparations that were manufactured prior to December 2019. Because we have limited amounts of this inventory remaining, we are reserving it for urgent cases until we are able to release the remainder of our inventory.
The announcement mentions that OpenBiome sold equipment and other assets. To whom? How did that process work? We sold some of our manufacturing equipment, software, and other assets to Finch Therapeutics Group, a microbiome therapeutics company with whom we have a longstanding collaboration. The challenging financial circumstances resulting from the pandemic made it necessary for us to take significant steps to ensure that patients would still have access to our FMT inventory.
Members of OpenBiome’s founding team launched Finch to help get a microbiome-based treatment for C. difficile approved by the FDA, a process that as a nonprofit, OpenBiome could not successfully undertake itself. In 2017, OpenBiome licensed intellectual property and materials to Finch in exchange for royalties and milestones on related products developed by Finch. This structure ensures that if Finch is successful, OpenBiome will have significant resources to invest in our nonprofit mission in the long-term.
The two organizations are independent entities, with independent boards and legal counsel. However, a small subset of OpenBiome’s board and management hold equity in Finch, in recognition of their role in assisting with its founding. Additionally, in July 2019, OpenBiome’s Executive Director, Carolyn Edelstein, married Finch’s CEO, Mark Smith, with whom she co-founded OpenBiome, alongside others.
Given these relationships, to ensure that any contracts and agreements between Finch and OpenBiome serve in the best interest of OpenBiome’s nonprofit mission, the negotiation of this transaction, like all agreements between the two organizations, was handled directly by an Independent Special Committee of OpenBiome’s Board of Directors. This independent committee, which was formed in 2016, consists only of individuals with no financial, managerial, or familial ties to Finch. The independent committee also retained outside legal counsel with specialized expertise in related parties’ transactions and nonprofit oversight. Massachusetts regulators were also informed of the transaction in advance of the sale.
Since OpenBiome has solved the SARS-CoV-2 testing issue, can you restart a manufacturing program? In principle we could, but as a practical matter, we do not have the financial resources to both continue operations and invest in restarting our manufacturing operations. Furthermore, we anticipate that when an analogous FDA-approved therapeutic becomes available in the near future, both the need for and the FDA policy supporting widespread access to investigational FMT outside of clinical trials will cease. This regulatory path has been defined in successive draft FDA guidance documents over the years, most recently in 2016. The potentially brief operating window makes it very difficult to successfully execute an expensive restart.
What does the future hold for OpenBiome? What’s next after stool banking? When we incorporated in 2013, we gave ourselves an aspirational name – the Microbiome Health Research Institute. It was a mouthful (hence the adoption of ‘OpenBiome’) but it spoke to our goal to accelerate the pace at which this new field of medicine resulted in real benefits for patients.
The first part of our mission is to provide safe access to FMT. We are serving this aim not only through the provision of the thousands of units in our inventory, but also by creating an open-source library later this year with information on FMT screening, preparation and use that will help institutional stool banking operations meet the demand for FMT after OpenBiome exhausts our inventory. In the long run, the work that we have done to date to deliver more than 55,000 FMT preparations, support the systematic collection of data across more than 50 clinical trials, and license our technology to be used in the pursuit of an FDA-approved microbial therapy for prevention of recurrent C. difficile, are all steps that we undertook to secure safe access to this therapy for patients today and in the future.
The second part of our mission is to catalyze research on the human microbiome. The research that we have supported through our own provision of FMT has shown promise for other indications, including ulcerative colitis, graft-versus-host disease, and others. When we look to where the field is headed, we are confident that, beyond the near-term arrival of FDA-approved microbial therapies derived directly from human donors, precision microbiota therapies lie ahead. Bringing about this future requires the discovery, classification, and isolation of human microbiota strains, as a foundation to support the development and delivery of targeted therapies of bacterial consortia. We believe that with a collection of over 100,000 aliquots of cryopreserved stool specimens from hundreds of volunteers, we can play an outsized role in developing, curating, protecting and providing access to strain libraries and insights developed from them.
We look forward to sharing additional announcements in the future about the work that OpenBiome will be doing to push this mission forward and support our growing understanding of how to translate the human gut microbiome into improvements for public health.